451 patients with advanced NSCLC aged between 70 and 89 years and a PS of 0 to 2 ,were randomised 1 to 1 between single agent therapy with either vinorelbine or gemcitabine and the doublet of carboplatin and paclitaxel. At progression or in case of excessive toxicity, both arms were switched to erlotinib 150 mg/d.

As you can see on this slide, there is a provocative doubling of median progression free survival from 3 months in the single arm therapy to 6.1 months in the carboplatine + paclitaxel arm.One-year PFS is 15% for the doublet versus 2% for the single agents

This improvement in PFS is reflected in the overall survival with a benefit of 4 months in median overall survival time for the doublet arm, with 45% vs 27% of patients surviving 1 year. As you can see, median overall survival time and one year survival time in the single agent arm were near those predicted by previous studies, in elderly patients whereas t he median survival time and one year survival in the doublet arm are as one would expect in a general population of ‘any age’, with advanced NSCLC and a PS 0 to 2.

Summary: Based on the results of the phase II study, a placebo controlled phase III trial was designed and conducted in the 1 st line setting for pts with non-squamous cell NSCLC. The trial randomized 842 pts to receive carbo/taxol with or without bevacizumab. Pts that were on the placebo arm were not allowed to cross over. Pts on the bevacizumab arm received carbo/taxol/bev x 6 cycles and then bevacizumab until progression. The primary endpoint of the trial is survival. This trial completed accrual in April 2004 and results of the trial are expected by the end of 2005. KEY POINT Key phase III data in NSCLC are expected this year.

KEY POINTS The interim report from this phase III trial indicates that the addition of bevacizumab to carboplatin/paclitaxel in previously untreated patients with advanced NSCLC confers a significant survival advantage. This is the first demonstration of a survival advantage in this patient population when a targeted therapy was added to standard chemotherapy. Notes:

INTEREST was an international, multicentre, randomised, open-label, parallel-group study of gefitinib vs docetaxel in patients with locally advanced or metastatic recurrent NSCLC who were pretreated with platinum-based chemotherapy. 1 A total of 1466 patients from 149 centres in 24 countries worldwide were randomised to gefitinib (250 mg/day orally) or docetaxel (1-hour 75 mg/m 2 infusion every 3 weeks). The primary objective was to compare OS between the groups with co-primary analyses to assess non-inferiority in the overall per-protocol population and superiority in patients with high EGFR-gene-copy number. Secondary endpoints compared progression-free survival (PFS), ORR, quality of life (QoL), disease-related symptoms and safety and tolerability for gefitinib and docetaxel. Exploratory endpoints included the efficacy outcomes in biomarker subgroups. Reference Kim et al. Lancet 2008; 372: 1809-1818.

INTEREST demonstrated non-inferiority of gefitinib relative to docetaxel in terms of OS in the overall study population, according to the pre-specified protocol criteria. The hazard ratio (HR) was 1.020 and the 96% confidence interval (CI) was 0.905, 1.150. This CI fell entirely below the non-inferiority limit of 1.154. 1 Median survival was 7.6 months for gefitinib and 8 months for docetaxel. 1 One-year survival rates for gefitinib and docetaxel were 32% and 34%, respectively. 1 In the co-primary analysis, s uperiority of gefitinib in patients with high EGFR-gene-copy number was not proven (HR 1·09, 95% CI 0·78–1·51; p=0·62; median survival 8·4 vs 7·5 months) (data not presented). Reference Kim et al. Lancet 2008; 372: 1809-1818.

However, a mong patients with EGFR mutation, PFS was longer for gefitinib compared with docetaxel. There was no significant difference in PFS between treatments among EGFR mutation-negative patients. 1 Reference Douillard et al. J Clin Oncol 2008; 26 (20 May Suppl): Abstr 8001.

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META-ANALYSIS Single agents vs doublets vs triplets * Trial excluded because the number of patients/arm is not available ** Patients excluded of published analysis although randomized (trials not analyzed in ITT) C Delbaldo et al., JAMA